Low concentrations of taxol cause mitotic delay followed by premature dissociation of p55CDC from Mad2 and BubR1 and abrogation of the spindle checkpoint, leading to aneuploidy

Amy E. Ikui, Huang Yang Chia-Ping, Tomohiro Matsumoto, Susan Band Horwitz

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Taxol is widely used for the treatment of human cancer. Its mechanism of action in cells is dependent on drug concentration. At low concentrations of Taxol (5-10 nM), cells exhibit aberrant mitosis, including aneuploidy, in the absence of mitotic arrest. At higher concentrations of Taxol (>20 nM), the cell cycle is blocked at metaphase by spindle checkpoint activation. Here we demonstrate that low concentrations of Taxol cause mitotic delay, and result in an aneuploid population of cells after exit from mitosis. Low concentrations of Taxol dissociated p55CDC-Mad2 or p55CDC-BubR1 complexes after mitosis, whereas high concentrations of Taxol sustained the protein complex formation leading to mitotic block. The induction of apoptosis and aneuploidy by low concentrations of Taxol may result from chromosome missegregation caused by spindle checkpoint defects.

Original languageEnglish (US)
Pages (from-to)1385-1388
Number of pages4
JournalCell Cycle
Volume4
Issue number10
DOIs
StatePublished - Oct 2005

Keywords

  • BubR1
  • HeLa cells
  • Mad2
  • Spindle checkpoint
  • Taxol
  • p55CDC

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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